ADRB2 and heart failure: Given that β1 but not β2ARs are downregulated in heart failure69–72 along with β2AR redistribution from the T-tubules to the cell crest, giving rise to cell-wide cAMP propagation in the failing cardiomyocyte73, it is conceivable that low efficacy β2AR activation even occurs in human heart failure patients and may contribute to the positive effect of carvedilol.